Bactericidal and fungicidal tin compounds

ABSTRACT

Tri-isobutyl-tin azide, (i-Bu) 3  SnN 3  is disclosed, as are certain bis-(azido-di-alkyl-tin)-oxides of the formula ##STR1## and a method for making them, as well as bactericidal and fungicidal agents comprising these biocidal tin compounds.

This is a division of application Ser. No. 853,854, filed Nov. 22, 1977,now U.S. Pat. No. 4,112,084.

The present invention pertains to certain triorganotin azides, tocertain bis-(azido-diorgano-tin)-oxides, to a method for making suchoxides, and to bactericidal and fungicidal agents containing compoundsof these types and having bactericidal and fungicidal activity. Suchagents are suitable for use as disinfecting agents, wood protectiveagents, for imparting bactericidal and fungicidal properties toplastics, building materials, or textiles, or for use as biocidalplants.

The high activity of triorganotin compounds against microorganisms suchas damaging fungi and bacteria is known. The tributyltin compounds, inparticular tributyltin fluoride and bis-(tributyltin) oxide, have provedto be particularly effective. The high activity of the tributyltincompounds against bacteria, however, is limited to gram-positivebacteria: against gram-negative bacteria they are considerably lesseffective. Tripropyltin compounds, which, however, because of theirpenetrating repulsive odor have found no practical employment, behaveexactly contrarily: they are strongly inhibitory of gram-negativebacteria and less so of gram-positive bacteria.

These observations, in connection with a series of further tests, haveheretofore led only to the conclusion that the biocidal behavior oftriorganotin compounds was determined by the chain-length of thehydrocarbon group bound to tin, whereas the nature of the substituentsnot bound by carbon to tin was only of subordinate significance for thebiocidal effect. [On this point, see A. Bokranz and H. Plum,Fortschritte der chemischen Forschung, Vol. 16, Part 3/4, pages 376-379,Springer Verlag, Berlin, Heidelberg, New York (1971).]

Diorganotin compounds having an effect worth mentioning againstmicroorganisms are only individually described, for example in GermanAuslegeschrift No. 25 26 711.

The present invention relates to biocidal and fungicidal agents whichare characterized by a content of at least one compound of the formula

    Bu.sub.3 SnN.sub.3                                         (I),

in which Bu is n-butyl or isobutyl, or of the formula ##STR2## wherein Ris alkyl having 3-5 carbon atoms. A method for making the compounds offormula II by reacting dialkyltin dichloride with equimolar amounts ofan alkali azide and an alkali hydroxide in polar solvents with stirringat room temperature is also discussed.

Preferred new active agents are:

Triisobutyl-tin azide, bis-(azido-di-n-propyl-tin)-oxide,bis-(azido-di-n-butyl-tin)-oxide, bis-(azido-di-i-butyl-tin)-oxide, andbis-(azido-di-n-pentyl-tin)-oxide.

Compounds having formula II are stannoxanes. It is known from theliterature that stannoxanes are in equilibrium with the correspondingorganotin hydroxides. The position of the equilibrium depends, amongother things, on the organic residue bound to tin and on the solvent[cf. W. P. Neumann, Die org. Chemie des Zinns, Ferd. Enke Verlag,Stuttgart (1967), Chapter 17.1, and A. K. Sawyer, "Organotin Compounds",M. Dekker, Ind., New York (1971) Chapter 4. 1A]. Thus, a simultaneouspresence of R₂ Sn(OH)N₃ in compounds having formula II cannot beexcluded, particularly if their preparation takes place in an aqueousmedium.

The compounds to be used as biocidal agents according to the presentinvention are insensitive to shock and impact. On dry heating, theyslowly give off nitrogen and decompose to a black-brown residue withouttendency toward explosion. Because of their difficult solubility inwater, the organotin azides show only a slight tendency to hydrolyze.

The preparation of the organo-tin azides takes place by the reaction oftriorganotin chlorides for diorganotin dichlorides with azides, forexample NaN₃, according to the following equations (1) and (2): ##STR3##

Reaction (2), in particular, involves the reaction of a dialkyl-tindichloride with substantially equimolar amounts of an alkali metalazide, such as sodium azide or potassium azide, and of an alkali metalhydroxide, such as sodium hydroxide or potassium hydroxide. The reactionproceeds at room temperature by stirring the reagents in a polar solventsuch as water; acetone (and in particular in mixtures of water andacetone); ethers, particularly diethyl ether; and alcohols, particularlymethanol and ethanol.

Surprisingly, the organotin azides which are to be employed according tothe invention and which can be prepared in a simple manner in part showa greater activity than the heretofore known tributyltin compounds ordiorgano-tin compounds. Further, their activity spectrum extends also tothe gram-negative bacteria.

The bactericidal and fungicidal efficacy of the organotin azides areevident from following Tables 1 and 2. Bis-(tributyltin) oxide (TBTO)was chosen as a substance for purposes of comparison.

For carrying out the biocidal test, nutrient agar was poured into petridishes having a diameter of 10 cm. After solidification of the agar, thepaper filters to be tested were placed thereon and sprayed with slurriesof test bacteria or test fungi.

Normalization of the concentration of the test bacteria or test fungiwas photometrically determined by means of a 1 cm-thick cuvette.

The extinction of the slurry was measured with a Zeiss PMQ 2spectrophotometer. At 420 microns, the following extinction values weremeasured against water: (Selection)

    ______________________________________                                        Aspergillus niger   0.5                                                       Penicillium funiculosum                                                                           0.8                                                       Bacillus mesentericus                                                                             1.3                                                       Bacillicus subtilis 1.3                                                       ______________________________________                                    

Subsequently the fungi were cultured for three weeks at 30° C. and thebacteria for 2 to 4 days at 37° C.

The biocidal effect was evaluated according to the strength of thegrowth as well as the size of the inhibition zone around the samples.

Preparation of the Samples

Round filters of 5.5 cm diameter were saturated with ethanolic solutionsof various concentrations and subsequently dried in air at roomtemperature.

Concentration of the azide on the filter:

2.0/1.0/0.5/0.2%

Test bacteria:

Bacillus subtilis ATCC 6633

bacillus mesentericus ATCC 945

escherichia coli ATCC 10 536

Test fungi:

Aspergillus niger CBS 420.64

pullularia pullulans BAH P 268

penicillium funiculosum CBS 170.60

Test media:

Biomalt-Agar 8° [measured in a Balling saccharometer at 20° C.] (forfungi)

Plate-count-agar (for bacteria)

                  Table I                                                         ______________________________________                                        Bacteria                                                                      Results:                                                                                   Zone of inhibition                                                            around the samples in mm.                                        Content of Active Agent                                                                      Bac. mes  Bac. subt. E. coli                                   ______________________________________                                        None                0         0       0                                       2.0%  TBTO         12-15     12-15    0-1                                     1.0%  "            10        12-15    0                                       0.5%  "             9-10     12-15    0                                       0.2%  "             8        12       0                                       2.0%  nBu.sub.3 Sn-azide                                                                         12-15     10       1                                       1.0%  "            12-15     10       0-1                                     0.5%  "            12-15     10       0                                       0.2%  "            10        10       0                                       2.0%  1-Bu.sub.3 Sn-azide                                                                        15        15       0                                       1.0%  "            15        12-15    0                                       0.5%  "            15        10-12    0                                       0.2%  "            12-15     10       0                                                         Zone of Inhibition                                                            around the samples in mm.                                                       Bac.                                                      Content of Active Agent                                                                           subt.  Bac. mes.                                                                              E. coli                                   ______________________________________                                        2.0%  Azido-(di-n-butyl-tin)-oxide                                                                    3      4-5    2-3                                     1.0%  "                 3      4      1-2                                     0.5%  "                 2-3    3-4    1                                       0.2%  "                 2-3    2-3    1                                       2.0%  Azido-(di-i-butyl-tin)-oxide                                                                    10     12-15  6-7                                     1.0%  "                 9      10     5                                       0.5%  "                 8      7-8    4                                       0.2%  "                 7-9    8      3-4                                     2.0%  Azido-(di-n-propyl-tin)-oxide                                                                   10     12-15  7                                       1.0%  "                 9      10     5-6                                     0.5%  "                 8      8      4                                       0.2%  "                 7      8      3-4                                     2.0%  Azido-(di-n-pentyl-tin)-oxide                                                                   9      13     6                                       1.0%  "                 8      9      4-5                                     0.5%  "                 7      8      4                                       0.2%  "                 6      7      3                                       ______________________________________                                    

                                      Table 2                                     __________________________________________________________________________    Fungi                                                                                   Asp. nig.                                                                           Zone of                                                                            Pull. pull.                                                                              Pen. fun.                                                                           Zone of                                 Content of                                                                              Growth on                                                                           Inhibition                                                                         Growth on                                                                           Zone of                                                                            Growth on                                                                           Inhibition                              Active Growth                                                                           Sample                                                                              (mm) Sample                                                                              Inhibition                                                                         Sample                                                                              (mm)                                    __________________________________________________________________________    0         ++++  0    ++++  0    ++++  0                                       2.0%                                                                             TBTO   -     5    -     3    -     1                                       1.0%                                                                             "      -     4-5  -     2-3  -     0--                                     0.5%                                                                             "      -     4    -     2    +R    0                                       0.2%                                                                             "      -     1    -     0-1  ++    0                                       2.0%                                                                             n-Bu.sub.3 Sn-azide                                                                  -     9    -10   -    1                                             1.0%                                                                             "      -     8-9  -     4    -     0-1                                     0.5%                                                                             "      -     3    -     1-2  -     0-1                                     0.2%                                                                             "      -     1    -     0    +R    0                                       2.0%                                                                             i-Bu.sub.3 Sn-azide                                                                  -     12-15                                                                              -     12-15                                                                              -     0                                       1.0%                                                                             "      -     10-12                                                                              -     12-15                                                                              I     0                                       0.5%                                                                             "      -     3-4  -     10-12                                                                              I     0                                       0.2%                                                                             "      -     1    -     3-4  I     0                                       __________________________________________________________________________     Legend:                                                                       - no growth;                                                                  + light growth;                                                               ++ moderate growth;                                                           +++ strong growth;                                                            ++++ very strong growth;                                                      R = edge growth;                                                              I = Test fungus became infected with a foreign fungus.                   

The organotin azides to be used according to the invention can beemployed alone, in admixture with each other, or in admixture with otheractive agents such as quaternary ammonium bases or phenolic compounds.

The organotin azides are suitably employed in the form of preparationssuch as solutions, dispersions, or with solid carriers or diluents,optionally in the presence of wetting agents, adhering agents,emulsifying agents, and dispersing agents. Suitable liquid carriers are,for example, methanol, ethanol, toluene, and xylene. As solid carriers,diatomaceous earth, siliceous clay, silica gel, kaolin, or talc aresuitable, for example. Suitable surface-active subtances are, above all,the non-ionic polyethylene glycols.

Suitable formulations are given below, with the percentages by weight:Tri-isobutyl-tin azide in toluene as a 2% solution; tri-n-butyl-tinazide with 3 parts of emulsifier comprising alkyl-aryl-polyglycol etheras a 1% aqueous emulsion; bis-(azido-di-n-butyl-tin)-oxide on talc as a2% strewable powder; bis-(azido-di-isobutyl-tin)-oxide as a 1% dilutionwith bleaching earth; and bis-(azido-di-n-pentyl-tin) oxide as a 5%solution in ethanol.

The agent can be applied in any desired fashion, for example byinjection, immersion, spraying, dusting or painting.

The concentration of the active material in the biocidal agent can varywithin relatively wide limits. It depends on the kind of themicroorganism to be combatted as well as on the substrate (wood,textiles, etc.). It is between about 0.1% and 3% by weight, based on thebiocidal agent. In the preventive treatment of substrates, smallerconcentrations would be chosen than when combatting microorganismsalready present. Since the organotin azides according to the inventionare only difficultly soluble in water, they can advantageously be usedoutdoors where they are exposed to weathering.

A better understanding of the present invention and of its manyadvantages will be had by referring to the following examples, given byway of illustration.

EXAMPLE 1

65.1 g of tri-isobutyl-tin chloride (0.2 mol) are dissolved in 100 ml ofether. This solution is run into another solution of 15.4 g of sodiumazide (0.237 mol) in 80 ml of water and 40 ml of acetone. After stirringfor one-half hour, the phases are separated. After driving off theether, a tri-isobutyl-tin azide product remains whose Cl-value is0-2.3%. The yield is ca. 80%. C found = 44.21% (theory = 43.41%); H =8.74 found (8.20 theory); n_(D) ²⁰ : 1.5009.

EXAMPLE 2

In a fahsion analogous to that above, the following materials werereacted: 30.38 g (0.1 mol) of di-isobutyl-tin-dichloride in 100 ml ofether and 15.4 g of sodium azide (0.237 mol) dissolved in water/acetone.After four hours' stirring, 4 g (0.1 mol) of NaOH were added. The solidwhite product precipitates in a yield of 26 g, which is 90% based on theformula i-Bu₂ (N₃)SnOSn(N₃)i-Bu₂. It melts at 172°-174° C. Elementalanalysis gave the following values [theoretical values are based oni-Bu₂ (N₃)SnOSn(N₃)i-Bu₂ ]: C: 33.69 (32.92) %; H: 6.65 (6.56) %; N:12.97 (14.39)%; Cl: 0.87 (0)%; Sn:41.70 (40.65) %.

EXAMPLE 3

Example 2 was repeated using di-n-butyl-tin dichloride to preparebis-(azido-di-n-butyl-tin)-oxide. The same yield was obtained. Themelting region was 75°-80° C. The elemental analysis was similar to thevalues given above.

EXAMPLE 4

30.38 g (0.1 mol) of di-i-butyl-tin dichloride are dissolved in about100 ml of methanol and poured into a suspension of 15.4 g of sodiumazide in methanol. After four hours' stirring, 4 g (0.1 mol) of NaOH areadded; thereafter a little toluene (50 ml) is added and the methanol,which dissolves small amounts of sodium azide, is distilled off. Theliquid is filtered off from the precipitated sodium salts and thetoluene is removed in vacuum. A product like that in Example 2precipitates in 97% yield (28 g).

EXAMPLE 5

27.6 g (0.10 mol) of di-propyl-tin-dichloride are dissolved in 100 ml ofether and let flow into a solution of 7.15 g (0.11 mol) of NaN₃ in 60 mlof water and 40 ml of acetone. After stirring for four hours at roomtemperature, 4 g of NaOH (0.1 mol) are added. The ether phase isseparated in a separatory funnel and freed of ether after drying overNa₂ SO₄. A solid white residue of bis-(azido-di-propyl-tin)-oxideremains in 24.2 g yield: that is 91.8% of theory. IR spectrum clearlyshows the azide band at 2080-2095 cm⁻¹. The sample melts at 87° C. butfirst clearly flows together only at 160° C. Analysis: C found = 28.53(27.30%); H = 5.69 (5.69); N = 13.78 (15.93%); Sn = 45.65 (45.01%).

EXAMPLE 6

33.2 of di-pentyl-tin dichloride is treated as in Example 5. The residueof bis-(azido-di-pentyl-tin)-oxide weighs 30 g (93.8% of theory). Itappears slightly yellowish and has a waxy consistency. Its flow point isbetween 59°-60° C. The IR-spectrum shows the azide bands at 2080-2095cm⁻¹.

Analysis: C found = 38.09 (37.53%); H = 7.43 (7.19%); N = 10.94(13.14%); and Sn = 37.11 (37.13%).

What is claimed is:
 1. The method of making abis-(azido-di-alkyl-tin)-oxide of the formula ##STR4## wherein R isalkyl having 3-5 carbon atoms, which comprises reacting a dialkyl-tindichloride of the formula R₂ Sn Cl₂ with substantially equimolar amountsof an alkali metal ozide and an alkali metal hydroxide at roomtemperature in a polar solvent.